Evolution and transmission of mosquito-borne viral zoonosis

Alphaviruses are a group of mosquito-transmitted RNA viruses that cause widespread human epidemics. The most notable example is chikungunya virus which causes crippling arthritic joint manifestations.

Despite the high genetic mutation rate of RNA viruses, alphaviruses undergo substantially slower rate of evolution than viruses that are directly transmitted from human to human, e.g. SARS-CoV-2.

The alternating transmission cycle from mosquito vector to human host probably constrains evolution event, but this is fundamentally understudied.

Therefore, the purpose of this study is to characterize alphavirus evolution mechanisms in a heterogeneous environment with mosquito and mammalian cellular barriers. This three-year project consists of three aims which are studied in parallel. The first aim focuses on mammalian adaptation in transmission events between mosquito and mammalian cells.

We use a unique cell assay that enables rapid screening of adapted viruses.

In the second aim, we identify evolutionary bottlenecks in mosquito organs using novel techniques like single-cell sequencing and an ex vivo mosquito midgut model. The third aim, targets alphavirus adaptation to another mosquito specie using advanced deep mutational scanning.

The proposed study will generate comprehension of molecular evolution processes, and the interactions between virus and mosquito to predict (re-)emerge of viruses, develop countermeasures like antivirals, and understand epidemiology.